The design and synthesis of new macromolecules for the preparation of hydrogels is one of the major challenges of modern polymer chemistry. A variety of polymeric hydrogels and their membranes are used in applications as diverse as gas separations, microfiltration, hyperfiltration, hemodialysis, electrodialysis, biocompatible coatings and controlled drug delivery. There is continuing need for new and improved hydrogels especially in biomedical engineering applications.
Hydrogels are polymeric networks which contain relatively large amounts of water. These types of materials have been investigated extensively for potential biomedical applications because of their similarities to soft tissues and their potential tissue and blood compatibility behavior. They are also of interest as membrane materials in both biological and non-biological applications and as surface coatings to generate highly hydrophilic surfaces. Of particular importance are ionic hydrogels because of their equilibrium degree of swelling is affected by changes in pH or ionic strength. These ionic hydrogels usually contain ionizable pendent groups such as carboxylic acid, sulfonic acid, or quaternized amino units. Because of their ionic nature, these hydrogels have special properties for use in membranes and in pH sensitive drug delivery systems. pH sensitive hydrogels with anionic groups, in particular, are especially promising for biomedical uses since these gels have been shown to be better bioadhesives than their cationic or neutral counterparts (see Br.o slashed.ndsted, H.; Kopecek, J. In Polyelectrolyte Gels; Harland, R. S.; Prud'homme, R. K., Ed.; ACS: Washington D. C., 1992; Vol. 480, p. 285; and Leung, S. S.; Robinson, J. R. In Polyelectrolyte Gels; Harland, R. S.; Prud'homme, R. K., Ed.; ACS: Washington D. C., 1992; Vol. 480, p. 269). Furthermore, it has been shown that anionic surfaces with high charge density generate improved blood compatibility (see Goggins, J. A. et al. In Advances in Biomedical Polymers; Gebelein, C. G., Ed.; Plenum Press: New York, 1987; Vol. 35, p. 215; and Helmus, M. N. et al. J. Biomed. Mater. Res. 1984, 18, 165).
For many biomedical applications, synthetic polymers are generally preferred over natural polymers for their reproducibility and ease of manufacture. Synthetic polymers are used increasingly in medical science due to the chemist's ability to incorporate specific properties such as strength, hydrogel characteristics, permeability or biocompatibility, particularly in fields like cell encapsulation and drug delivery where such properties are often prerequisites. However, harsh conditions, e.g., heat or organic solvents, are usually used when encapsulating with these polymers often causing difficulties in encapsulating sensitive entities, e.g. proteins, liposomes, and mammalian cells.
A number of different polymers have been used for controlled drug delivery. Some examples include the biodegradable polymers poly(anhydrides), poly(orthoesters), and poly(lactic acid) and the non-degradable polymers ethylene vinyl acetate and poly(acrylic acid). Various polyphosphazene polymers have also been shown to be useful for controlled drug delivery. For example, U.S. Pat. No. 4,880,622 to Allcock et al. and U.S. Pat. No. 5,053,451 to Allcock et al. (both incorporated herein by reference) disclose polyphosphazene polymer hydrogels including their use as drug delivery devices formed by standard techniques including: dissolution and casting of the polymer into a film or disk, dissolution of the polymer and cross-linking by covalent bonding or by irradiation to form a soft gel, and compression of polymer particles into a disk.
Synthetic polymers are also widely used for membrane applications. The synthetic polymers currently used as membranes can be divided into two categories: (1) neutral polymers such as polyethylene, poly(methyl methacrylate), poly(organosiloxanes), and cellulose acetate, and (2) ionic polymers such as poly(acrylic acid), sulfonated polystyrene, and perfluorinated ionomers. The consideration of a polymer for incorporation into membranes involves a subtle balancing of properties such as hydrophilicity, molecular weight, crystallinity, polarity, mechanical strength, and the solvation-type affinity between specific polymers and small molecule solutes or gas molecules. In these terms, the tailoring of sophisticated membrane systems is still in its infancy. For this reason, poly(organophosphazenes) are especially attractive as candidates for membrane applications.
In prior publications, we have reported that the macromolecular substitutive synthesis of poly(oranophosphazenes) allows the properties of these polymers to be varied over a wide range by the incorporation of different substituent groups (R) Allcock, H. R. Chem. Eng. News 63,22 (1985)!. These property changes can be orchestrated with great subtlety both by varying the R group in single substituent polymers and by the use of two or more cosubstituent groups attached to the same chain. In this way individual polymers may be hydrophobic, amphiphilic, or hydrophilic; water-stable or water-erodable; crystalline or amorphous; or bioinert or bioactive. Our previous work has demonstrated methods for the radiation cross-linking of specific polyphosphazenes in order to optimize their behavior as membranes or hydrogels see, for example, Allcock, H. R. et al. Biomaterials 19, 509 (1988)!.